Thank you very much for your assistance !
By doing the same transformation in vacuum, I did obtain a value of -22.86 +/- 0.03 kcal/mol that, when susbtracted from my original value, gives me the expected result of ~6 kcal/mol. I do admit that, even though it seems logical to me it is required to close the thermodynamic cycle, I thought this vacuum transformation would lead to a value of 0, since there is no solvent to interact with. I did not expect such a value, that seems high for a molecule interacting with itself, but I think I’m mixing some things up…
Just as a side note, I also tried with couple_intramol=no and the values are almost unchanged ( -29.30 +/- 0.03 kcal/mol and -29.34 +/- 0.03 kcal/mol). I looked again on the forum for topics about this parameter and found this clear answer by J.Lemkul : Relationship between couple-moltype and couple-intramol - #5 by jalemkul
I’m quoting him directly (I don’t know if there is a better way to do it):
couple-intramol is integral to the calculation, it specifies whether intramolecular force field terms are coupled as a function of λ. For an absolute free energy calculation, it needs to be set to no but for a transformation like you’re describing, in which the molecular structure changes, it should be set to yes.
Anyway, thanks again !